4-Biphenylcarbonylacylamido penicillanic acid and salts

ABSTRACT

The invention provides anti-bacterial agents of the formula:   IN WHICH M is a member selected from the group consisting of -H, an alkali metal and -NH4.

United States Patent [191 Wei et al.

[ July 8,1975

[ 4-BIPHENYLCARBONYLACYLAMIDO PENICILLANIC ACID AND SALTS [75] Inventors: Peter H. L. Wei, Springfield; Ronald J. McCauIiy, Malvern, both of Pa.

[73] Assignee: American Home Products Corporation, New York, NY.

[22] Filed: Mar. '18, 1974 [2]] App]. No: 452,016

[52] US. Cl 260/2391; 424/271 FOREIGN PATENTS OR APPLICATIONS 877,531 9/1961 United Kingdom 260/239.l

Primary Examiner-Gerald A. Schwartz Attorney, Agent, or FirmRichard K. Jackson [57] STRACT The invention provides anti-bacterial agents of the formula:

[51] Int. Cl. C07D 499/44 [58] Field of Search 260/239.1

[56] References Cited UNITED STATES PATENTS 3,360,527 12/1967 Naito et al. 260/239.l X

in which M is a member selected from the group consisting of H, an alkali metal and NH 2 Uaims, No Drawings 4 -ERlPHENYLCARBONYLACYLAMlHDJQ EXAMPLE I PENHQHLLANH AUID AND SALTS 6-[3-(4-Biphenylylcarbonyl) acrylamido] penicillanic 'd. Alpha, beta-unsaturated amides of 6- acl aminopenicillanic acid are disclosed in British Pat. No. 5 To a tetrahydrofuran solution Containing biphenylylcarbonyl)acrylic acid in a salt-ice bath is DESCRHPTHON OF THE TI N added triethylamine (0.50 g.), followed by an equimolar amount of isobutyl chloroformate. After the solu- In accordance with this invention there is provided a I tion is stirred for 15 minutes, a cold solution of aqueous group of anti-bacterial agents which are 6-[3-(4- 10 biphenylyl-carbonyl)acrylamido] penicillanic acid, the tetrahydTofuran Containing an equlmolal amount of alkali metal and ammonium salts. aminopenicillanic acid and 0.50 gram of triethylamine,

The compounds of the invention are prepared by is added. The mixture is stirred in the ice bath for 1 ccupllng hblphenylylcarbonylacrylic acid with hour and at room temperature for an additional hour.

aminopenicillanic acid or a salt thereof by the mixed anhydride or dehydrative coupling method as it is con ventionally employed in polypeptide synthesis. Alter- A small amount of solid material is removed by filtration and the filtrate is evaporated under reduced presnatively, the 4-biphenylylcarbonylacrylic acid halide Sure at faPProxlmately 30C The resldue 1s i may be produced by conventional techniques and in 50 milliliters H O, filtered and the filtrate 1s acldlfied acted with o-aminopenicillanic acid or salt in the preswith 6N The wsulting precipitate is Washed with ence of an acid acceptor. water, dissolved in ethyl acetate and dried over anhy- The anti-bacterial agents of this invention are notedrous MgSO The solvent is removed and the residue for their activity against PeniCillin resistant is washed with pentane and collected as the title comstaphlococcus strains Cl-1P and 53-180, although they pound are also effective inhibitors for use in control of grampositive and gram-negative bacterium. The activity of Elemental Analysis: 24 22 2 5 2 the compounds was established in accordance with the Calcd: C, 61.53; 1-11, 5.16; N, 5.98. well known, scientifically accepted agar serial dilution Found: C, 61.05; 1-1, 4.99; N, 6.31.

method for testing anti-bacterial agents. The compounds of the invention, having been proven effective antibacterial agents, are useful in the treatment of bacterial infections amenable to penicillin treatment. In Bacillus subtilis 6633 addition, the antibacterial agents of this invention are l t Spams 9955 125 f l th M f t. h l d Nelsserla catarrhalis 8193 15.6 use 1n e he s o compara ive p armaco ogy an staphylococcus aureus 6538p .976 in microbiology for the control and comparative analy staphylococcus aureus SMITH 976 515 Of bacterial colonies. Staphylococcus aureus CHP 31.3 The following example illustrates the preparation of Staphylococcus aureus 53-180 the free penicillanic acid, from which the sodium, po tassium and ammonium salts are produced by conventional means, as by reaction with potassium or sodium What is claimed is:

Z-ethylhexanoate or ammonium hydroxide. The activ- 11, A om und of the formula;

s /,CH. cocu cuconu ten ity of the free acid against specific bacterial strains is in which M is a member selected from the group conprovided for those bacterium completely controlled at i ti f ]1-{, an alk li t l d -NH a conce lr iitlration of 25ft) microgramsper milliliter and The compound f Claim 1 which i 3 4- below' produc? O the exdmp dcnve at hlgher biphenylylcarbonyl)acrylamido1penicillanic acid. concentrations against other bacterium. 

1. A COMPOUND OF THE FORMULA:
 2. The compound of claim 1 which is 6-(3-(4-biphenylylcarbonyl)acrylamido)penicillanic acid. 